Integrins and Ion Channels: Molecular Complexes and Signaling

Interdisciplinarity is more often invoked than practised. This is hardly surprising, considering the daunting vastness of modern biology. To reach a satisfactory understanding of a complex biological system, a wide spectrum of conceptual and experimental tools must be applied at different levels, from the molecular to the cellular, tissue and organismic. We believe the multifaceted regulatory interplay between integrin receptors and ion channels offers a rich and challenging field for researchers seeking broad biological perspectives. By mediating cell adhesion to the extracellular matrix, integrins regulate many developmental processes in the widest sense (from cell choice between differentiation and proliferation, to tissue remodeling and organogenesis). Rapidly growing evidence shows that frequent communication takes place between cell adhesion receptors and channel proteins. This may occur through formation of multiprotein membrane complexes that regulate ion fluxes as well as a variety of intracellular signaling pathways. In other cases, cross talk is more indirect and mediated by cellular messengers such as G proteins. These interactions are reciprocal, in that ion channel stimulation often controls integrin activation or expression. From a functional standpoint, studying the interplay between integrin receptors and ion channels clarifies how the extracellular matrix regulates processes as disparate as muscle excitability, synaptic plasticity and lymphocyte activation, just to mention a few. The derangement of these processes has many implications for pathogenesis processes, in particular for tumor invasiveness and some cardiovascular and neurologic diseases.

About the author (2010)

ANDREA BECCHETTI, PhD, is Professor of General, Comparative and Cellular Physiology at the Department of Biotechnology and Biosciences of the University of Milano-Bicocca, Italy. After receiving his academic degrees at the University of Milan, he has spent prolonged research sojourns at the Department of General Pathology of the University of Florence, Italy, the Department of Physiology at Emory University in Atlanta, Georgia, USA, the Department of Physiological Sciences of the University of Newcastle upon Tyne, UK, and the Biophysics Sector of the International School for Advanced Studies (ISAS-SISSA), in Trieste, Italy.His current research interests include the role of ion channels in cell adhesion and proliferation, the nicotinic modulation of synaptic transmission in the mammalian cerebral cortex and the pathogenesis of sleep-related epileptic forms linked to mutant human nicotinic receptors. Andrea Becchetti is member of the Society of General Physiologists, Biophysical Society, Society for Neuroscience and the Italian Physiological Society.

ANNAROSA ARCANGELI, MD, PhD is Professor of General Pathology and Immunology at the Department of Experimental Pathology and Oncology of the University of Firenze (Florence, Italy). She is the Scientific Director of the Laboratory of Genetic Engineering for the Production of Animal Models of the University of Firenze. After receiving her MD degree at the University of Firenze, she spent several research sojourns at the Department of Physiology of the University of Milano, at the Institut d’Embriologie Cellulaire et Moleculaire, Nogent sur Marne, Paris, France and at the MRC-LMB Centre of Cambridge, UK. Her main research interests include the role of ion channels, in particular potassium channels, in the regulation of different aspects of tumor cell behaviour, including the cross talk with adhesion receptors, as well as the identification of ion channels as novel targets for cancer therapy. Annarosa Arcangeli is member of the Italian Society of Pathology, the Association of Cell Biology and Differentiation (ABCD), the American Society of Hematology.